The biological function of the acute phase, C-reactive protein (CRP) remains unknown, despite the description of a number of in vitro reactivities with elements of the immune system. They include activation of the complement system, enhancement of phagocytosis, inhibition of platelet release reactions, and interactions with sub-populations of T-lymphocytes. A number of observations suggest that at least some of the biological activities of CRP might depend on its ability to interact with phospholipids: 1) CRP in serum is bound to lipid in the form of Ca ions dependent complexes, 2) deposits of CRP associated with membrane structures are found at inflammatory sites, 3) complexes of CRP with lecithin can efficiently activate complement, and 4) inhibition of platelet aggregation is probably mediated through interference with prostaglandin metabolism. Recently, we have observed that CRP can interact with model membranes probably causing releasing of phospholipid from the lipid bilayer. The potential importance of these preliminary observations for understanding the role of CRP in the regulation of acute inflammatory processes is obvious. Several mediator systems which require phospholipid for their activation and/or modulation might be influenced by CRP. Such phospholipid-dependent processes include activation of the clotting system, platelet release reactions, prostaglandin synthesis, and probably control of complement activation. This proposal constitutes an initial approach to the study of CRP-phospholipid interactions at the molecular level. Both the biochemistry and the biological significance of these interactions will be examined. Specifically, we propose to investigate; 1) the interactions of CRP with the phospholipids of artificial and natural lipid bilayers as well as serum lipoproteins, 2) the effects of these interactions on the modulation of effector systems of inflammation. An understanding of the CRP-phospholipid interactions will shed insight on the function of this acute phase protein.